The University of Louisville Molecular Targets Center of Biomedical Research Excellence (MT-COBRE) is focused on identification of novel molecular targets for cancer therapy, emphasizing structural biologic approaches for development of novel therapeutics. The overall objective of the MT-COBRE is to recruit and ensure the success of junior investigators who are members of the Molecular Targets Program at the UofL's Brown Cancer Center. We have made considerable progress towards accomplishment of the goals of the original application during the first five year funding period. Four of the original five COBRE scientists have received NIH R01 funding, the fifth was encouraged to pursue other directions. Five outstanding new scientists have taken their places, three of whom have NIH R01 applications under review or being revised for resubmission. We have been quite fortunate, during the initial funding period, to have retained all of the MT-COBRE faculty. We have leveraged the MT-COBRE support to create a set of effective Core Facilities which have significantly enhanced the productivity of the MT-COBRE investigators and other Brown Cancer Center scientists. The renewal application has added a new Core, the Biophysics Core Facility, and deleted a Core which was underutilized, the Proteomics Core Facility. The specific aims of the proposal are to: 1. develop successful independent research careers for each of the principal investigators that will lead to independent R01 grants. 2. develop core facilities that will enhance the research capability of the principal investigators and the other members of the MT program. 3. continue to develop the Molecular Targets Program as a cohesive research program which will enhance collaborative research projects and funding opportunities. 4. develop a nationally and internationally recognized program which will attract the very best graduate students, postdoctoral fellows and additional faculty. 5. make discoveries leading to new and more effective treatments for patients with cancer. During the next funding period, the MT-COBRE will utilize focused recruitment to enhance the scope of the program. Funding of this renewal application is critically important to allow the program to achieve its potential. Based on its current faculty and projected growth during the next funding period, this program is poised to become one of the nation's premiere cancer drug development programs.